Analyte determination methods and devices

ABSTRACT

The present invention provides methods and apparatuses for analyte detection.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional Application No.60/941,152, filed May 31, 2007, which application is incorporated hereinby reference.

BACKGROUND OF THE INVENTION

The detection of the level of analytes, such as glucose, lactate,oxygen, and the like, in certain individuals is vitally important totheir health. For example, the monitoring of glucose is particularlyimportant to individuals with diabetes. Measurement of glucose levels isan essential part of diabetes treatment and monitoring, and glucoselevels must be constantly monitored so that a diabetic can properlymaintain a normal glucose levels and avoid the ill effects of diabetes.To this end, a variety of blood glucose monitoring devices has beendeveloped to help people with diabetes maintain healthy levels of bloodglucose. In some devices, a test strip is used to obtain a sample ofblood for measurement of the glucose concentration in the sample. Thetest strip is then inserted into the blood glucose monitoring device,where the concentration of glucose in the blood is measured. The levelis then interpreted as either within, above, or below a recommendedlevel, so that the diabetic can take corrective action, if necessary.

Obtaining an accurate blood glucose reading is essential to those withdiabetes. If the measurement is inaccurate, the user might takeincorrect action to maintain proper blood glucose level, leading to ahost of immediate and long-term health problems.

Unfortunately, many factors affect the blood glucose measurement and cancause inconsistent readings. One of these factors is hematocrit, thevolume percentage of erythrocytes (red blood cells) in whole blood. SeeDorland's Illustrated Medical Dictionary (1974).

Hematocrit levels affect the measurement of blood glucose in severalways. One way is through the effect of hematocrit on blood viscosity.Blood viscosity strongly correlates to hematocrit levels, as the greaterthe percentage of blood cells in the total blood volume, the moreviscous the blood. The viscosity of blood then directly impacts glucosemeasurements, as these measurements are directly affected by the rate atwhich analytes and reagents diffuse within a sample chamber, and thisrate of diffusion is inversely related to viscosity.

For example, in amperometric measurement methods (which measures thecurrent being passed through a solution to determine the concentrationof an analyte), low hematocrits are typically coupled to elevatedglucose readings (and vice versa) for two reasons: (1) reduced viscosityincreases the mobility of both glucose and the soluble reagents employedto react with it, and (2) reduced oxygen concentration lessens thepercentage of electrons originating from glucose which ultimately aresidetracked to oxygen reduction. Both effects result in increasedcurrent, and therefore in elevated blood glucose readings. For highhematocrits, blood glucose readings are depressed, as (1) increasedviscosity impedes the mobility of glucose as well as reacting stripreagents, and (2) additional glucose-derived electrons are shunted tooxygen.

More advanced testing techniques use coulometry, where the analyteconcentration is determined by measuring the total charge consumed orproduced during an electrolysis reaction. In coulometric methods,especially those employing an oxygen-insensitive enzyme, both the abovesources of error are reduced. Nevertheless, coulometric methods mayretain some hematocrit influence. Furthermore, as strip test timesdecrease to below 5 seconds, a further source of hematocrit dependencepeculiar to coulometric methods may become significant. At very rapidtest times, glucose stored inside the erythrocyte may not substantiallydiffuse out of the cell during the assay, leading to increasedhematocrit influence.

Furthermore, hematocrit can vary significantly amongst individuals,which leads to inaccurate measurements of blood glucose in methods thatprovide a universal algorithm to correct for hematocrit dependence.

It is therefore desirable to know the hematocrit in a blood sample, sothat a suitable correction can be applied to the blood glucose readingto increase its accuracy. Some efforts to measure hematocrit and correctblood glucose levels based on these measurements have been made;however, most current methods rely upon interelectrode impedancemeasurements. Impedance measurements are vulnerable to artifacts arisingfrom incomplete filling and variations in electrode area and chamberthickness. Impedance measurements are also subject to interpersonalvariation in blood conductivity due to non-hematocrit related effectssuch as varying salt concentrations. Additionally, to determine ahematocrit electrochemically, a second electrochemical measurement mustbe completed after the initial measurement for glucose concentration,which adds time to the testing process.

In addition, current technology typically requires a manualdetermination of whether the sample is of a control solution or a bodilyfluid, such as blood. This can be problematic for several reasons; inparticular, a patient's poor eyesight or lack of dexterity can make amanual selection to indicate whether the solution is a sample or controlsolution quite difficult. An error in this manual entry will result inan erroneous average, which can significantly affect a patient's choiceof treatment options. For many patients, such manual interventionpresents a substantial physical challenge. A distinct issue unrelated tothe physical challenge of making such a manual adjustment, is thatindividuals who are responsible for showing their average glucose (acurrent function of most monitors) might willfully adjust their averageglucose readings by using the low or normal glucose level controlsolution, and in this way lower, their average glucose level. Such asituation may be encountered when an individual's own actions wouldrender the actual average glucose levels higher than desired. To furtherillustrate this example, when a teenager consumes food or beverages thatviolate a strict diet plan, he or she might be able to falsify theaverage glucose reading by substituting the blood sample with the low ornormal glucose level control solution. Thus, manual determination of acontrol solution remains a substantial problem in patient care.

Therefore, what are needed are improved methods and devices for accuratemeasurement of blood glucose concentration and determination of acontrol solution. Of interest are methods and devices for measuringhematocrit in a sample to correct for hematocrit dependence.

SUMMARY OF THE INVENTION

Embodiments of the present invention provide for the aforementionedproblems and fill the aforementioned needs by providing methods andapparatuses for determining a hematocrit-corrected value of an analytein a sample by determining the fill time of the sample on a test strip.Some embodiments of the present invention also provide methods andapparatuses for hematocrit correction in blood glucose concentrationmeasurements by using fill times of test strips to estimate thehematocrit and provide corrected blood glucose concentrations that aremore accurate and less dependent on the hematocrit. Some embodiments ofthe present invention also provide methods for determining whether asample is a control solution based on the hematocrit level in the sampleby using fill times of test strips to estimate the hematocrit andprovide determination that the sample is a control solution. Alsoprovided are systems and kits.

BRIEF DESCRIPTION OF THE DRAWINGS

The accompanying drawings, which are incorporated in and constitute apart of this specification, exemplify the embodiments of the presentinvention and, together with the description, serve to explain andillustrate principles of the invention. The drawings are intended toillustrate major features of the exemplary embodiments in a diagrammaticmanner. The drawings are not intended to depict every feature of actualembodiments nor relative dimensions of the depicted elements, and arenot drawn to scale.

FIG. 1 is a graph depicting a correlation between a hematocrit level andviscosity in blood.

FIG. 2 is an exploded-view illustration of an embodiment of a test stripfor the measurement of blood glucose which is capable of determining ahematocrit value based on the fill time of the test strip.

FIG. 3A is an illustration of an embodiment of an electrodeconfiguration in the test strip measuring the fill time of a sample ofblood in order to determine a hematocrit value.

FIG. 3B is an illustration of an embodiment of an electrodeconfiguration in the test strip after a sample of blood has completelyfilled the test strip.

FIG. 4 is a graph depicting a hematocrit dependence of fill time in atest strip embodiment for a physiological sample.

FIG. 5 is a graph depicting a linear regression slope of hematocritdependence according to embodiments of the present invention.

FIG. 6 is a graph depicting a corrected linear regression slope afterresponse data from a glucose measurement was corrected to lessen thehematocrit dependence according to embodiments of the present invention.

DETAILED DESCRIPTION OF THE INVENTION

Before the present invention is described, it is to be understood thatthis invention is not limited to particular embodiments described, assuch may, of course, vary. It is also to be understood that theterminology used herein is for the purpose of describing particularembodiments only, and is not intended to be limiting, since the scope ofthe present invention will be limited only by the appended claims.

Where a range of values is provided, it is understood that eachintervening value, to the tenth of the unit of the lower limit unlessthe context clearly dictates otherwise, between the upper and lowerlimit of that range and any other stated or intervening value in thatstated range, is encompassed within the invention. The upper and lowerlimits of these smaller ranges may independently be included in thesmaller ranges is also encompassed within the invention, subject to anyspecifically excluded limit in the stated range. Where the stated rangeincludes one or both of the limits, ranges excluding either or both ofthose included limits are also included in the invention.

Unless defined otherwise, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which this invention belongs. Although any methods andmaterials similar or equivalent to those described herein can also beused in the practice or testing of the present invention, the preferredmethods and materials are now described. All publications mentionedherein are incorporated herein by reference to disclose and describe themethods and/or materials in connection with which the publications arecited.

It must be noted that as used herein and in the appended claims, thesingular forms “a”, “an”, and “the” include plural referents unless thecontext clearly dictates otherwise.

The publications discussed herein are provided solely for theirdisclosure prior to the filing date of the present application. Nothingherein is to be construed as an admission that the present invention isnot entitled to antedate such publication by virtue of prior invention.Further, the dates of publication provided may be different from theactual publication dates which may need to be independently confirmed.

As will be apparent to those of skill in the art upon reading thisdisclosure, each of the individual embodiments described and illustratedherein has discrete components and features which may be readilyseparated from or combined with the features of any of the other severalembodiments without departing from the scope or spirit of the presentinvention.

The figures shown herein are not necessarily drawn to scale, with somecomponents and features being exaggerated for clarity.

Embodiments of the present invention provide methods and apparatuses fordetermining a hematocrit-corrected value of an analyte in a sample bydetermining the fill time of the sample on a test strip. In onenon-limiting embodiment, the method provides for hematocrit correctionin a blood glucose concentration measurement by using the fill time of atest strip to estimate the hematocrit and provide a corrected bloodglucose concentration that is more accurate and less hematocritdependent. In another non-limiting embodiment, the method provides fordetermining whether a sample is a control solution by using fill timesof test strips to provide a determination that the sample is a controlsolution. Since a control solution is equivalent to a blood sample withvery low or no hematocrit and therefore the control solution will fillthe test strip rapidly. The strong correlation between fill time of aphysiological sample in a test strip and hematocrit provides an accuratehematocrit measurement technique, especially when small test volumes areused and quick fill times are needed. The hematocrit correction isparticularly beneficial in diabetes self-monitoring, where diabetics areconstantly seeking advanced testing equipment that provides moreaccurate results, requires smaller blood samples and less time tocomplete the test.

Blood viscosity is a very strong function of hematocrit, as shown in thegraph depicted in FIG. 1 (Am. J. Physiol., 1992, 263, H1770-1778). Asnoted by the plotted line 102, as viscosity of blood 104 increases, sodoes the percentage of hematocrit 106. The dependence of viscosity onhematocrit continues and becomes even more pronounced at higherhematocrits.

Likewise, the rate at which glucose test strips fill is highly dependenton viscosity. Therefore, strip fill time is also a strong function ofhematocrit. Low hematocrit samples fill rapidly, and high hematocritsamples fill slowly. For example, a control solution is equivalent to ablood sample with very low or no hematocrit and therefore the controlsolution will fill the test strip rapidly. A control solution isgenerally an aqueous solution that contains a known amount of analyte,such as glucose, and is equivalent to a blood sample with very low or nohematocrit.

Embodiments of the test strips 108, as illustrated in, for example, theexploded-view embodiment of FIG. 2, measure analyte concentrations usingelectrochemical techniques. Other techniques are contemplated as well.Embodiments include coulometric and amperometric systems. Embodimentsare described herein primarily with respect to coulometric systems,where such descriptions are exemplary only and are in no way intended tolimit the scope of the invention. It is also to be understood thatembodiments are described primarily with respect to glucose systems inwhich glucose is the analyte of interest. It is to be understood thatembodiments include other analytes. For example, analytes that may bemonitored include, but are not limited to, acetyl choline, amylase,bilirubin, cholesterol, chorionic gonadotropin, creatine kinase (e.g.,CK-MB), creatine, creatinine, DNA, fructosamine, glucose, glutamine,growth hormones, hormones, ketone bodies, lactate, peroxide,prostate-specific antigen, prothrombin, RNA, thyroid stimulatinghormone, and troponin. The concentration of drugs, such as, for example,antibiotics (e.g., gentamicin, vancomycin, and the like), digitoxin,digoxin, drugs of abuse, theophylline, and warfarin, may also bemonitored. In those embodiments that monitor more than one analyte, theanalytes may be monitored at the same or different times on the same ordifferent test strip.

Any suitable analyte monitoring system may be employed. Systemstypically include an analyte test strip and a test strip meter used toread the test strip. For example, analyte monitoring systems that onlyrequire small sample sizes, e.g., about 1 microliter or less, e.g., lessthan about 0.5 microliters, e.g., less than about 0.25 microliters orless, e.g. less than about 0.1 microliters, are contemplated. Shortassay time analyte monitoring systems are also contemplated, e.g.,systems in which an analyte value may be obtained in about 20 seconds orless, e.g., about 10 seconds or less, e.g., about 5 seconds or less,e.g., about 3 seconds or less. Certain embodiments include Precision®and FreeStyle® blood glucose monitoring systems available from AbbottDiabetes Care, Inc. (Alameda, Calif.). Descriptions of test strips,meters and systems of use in embodiments of the invention may be foundin, e.g., U.S. Pat. Nos. 6,071,391; 6,120,676; 6,143,164; 6,299,757;6,338,790; 6,377,894; 6,600,997; 6,773,671; 6,514,460; 6,461,496;6,503,381; 6,591,125; 6,592,745; 6,616,819; 6,618,934; 6,676,816;6,749,740; 6,893,545; 6,942,518; 6,592,745; 5,628,890; 5,820,551;6,736,957; 4,545,382; 4,711,245; 5,509,410; 6,540,891; 6,730,200;6,764,581, and elsewhere.

Generally, the test strip meter is equipped with a connector designed tohouse the test strip and further consisting of contact points configuredto contact conductive pads on a distal end of the test strip. When thetest strip is inserted into this connector, electrical contact is madeand the meter may recognize the act of test strip insertion and turnitself on. Alternatively the user may press a button to turn the meteron.

After the meter is turned on, a blood sample 110 or control solution isintroduced into the test strip 108 as illustrated in FIG. 2. The teststrip 108 may or may not contain a means for determining that the bloodor control solution has completely filled the strip. The meter appliesan active potential to a working electrode 112 on the test strip 108,sufficient to initiate the oxidation of glucose (through the agency of amediator and an enzyme 114). This potential may be applied as soon asthe test strip 108 is inserted into the meter, or it may commence onlyafter the test strip 108 is deemed full. After this active potential isapplied, electrons originating from glucose in the sample are injectedinto the working electrode 112, then pass through the meter, where theyare counted.

The measurement is in the form of a recorded current versus time. Thismeasurement is continued until such time as the measurement is deemedcomplete, generally by logical comparison of the recorded current/timecurve with a set of conditions stored in the meter software. Theseconditions might include any of the following (or others): (1) timesince current flow began, (2) time since strip deemed full, (3) currentas a percentage of peak current, (4) time since peak current, etc. Whenthe set of logical conditions is met, current measurement ceases, andthe meter uses its internal logic to calculate a glucose value. This maybe accomplished by measuring the current at cessation of measurement,the integrated current (charge) over the lifetime of the measurement, orsome hybrid of these two approaches. The meter calculates a singlecurrent or charge characteristic of the glucose measurement, and insertsthis value into an internal equation to calculate a glucose value. Thecalculated glucose value is then displayed by the meter.

For certain blood glucose test strips, such as the embodimentillustrated in FIG. 2, the fill time is available from electrochemicalcurrent measurements using a working electrode and a counter-referenceelectrode displaced along the axis of sample flow, wherein one of theelectrodes is divided into at least two sub-electrodes whose current canbe measured independently. FIG. 2 shows a strip configuration in whichthe counter-reference electrode 116 (that electrode which passes acurrent equal in magnitude, but opposite in sign to the workingelectrode) is divided into three independently measurablesub-electrodes; designated a first sub-electrode 118, secondsub-electrode 120, and third sub-electrode 122. In another embodiment(not shown), the working electrode 112 is divided into sub-electrodesinstead of the counter-reference electrode. In a further embodiment, thecounter-reference electrode 116 or working electrode 112 is divided intoonly two sub-electrodes. The test strip 108 of the present aspect alsoincludes a bottom layer 124, usually plastic, and adhesive layer 126 inthe middle to hold the various components in place, and a top layer 128,usually plastic.

In another embodiment (no shown), a three electrode cell is used,containing a working electrode, a counter electrode, and a referenceelectrode. In this embodiment, either the working electrode or counterelectrode is divided into sub-electrodes for measuring the fill time.The reference electrode could be used to determine fill time, but themechanism would be different that previously described, as the referenceelectrode carries no current. In one embodiment the fill time detectionon the reference electrode could be potentiometric, wherein thesub-electrodes detect the presence of a potential on the referenceelectrode.

FIG. 3A illustrates the process by which the strip 108 fills with blood110 or control solution, sequentially contacting the threesub-electrodes. First, blood 110 enters a strip sample area 130,contacting the counter-reference electrode 116. Since thecounter-reference electrode is divided into three independentsub-electrodes, the first sub-electrode 118 is contacted first. Theblood 110 or control solution continues across the strip sample area130, next contacting the second sub-electrode 120. Finally, the blood110 or control solution finishes filling the strip sample area 130, asillustrated in FIG. 3B, contacting the third sub-electrode 122. At eachsub-electrode, the time at which the blood sample 110 or controlsolution contacts the sub-electrode is measurable by the onset ofcurrent through that particular sub-electrode. In this way, the timerequired for blood or control solution to cross the constant and wellknown inter-electrode distances can be calculated. Other test stripconfigurations may be used as well. Fewer or greater electrodes thanthose described herein may be employed. At least two sub-electrodes areneeded to measure the hematocrit fill time, from either the working orcounter-reference electrodes, although two sub-electrodes of bothelectrode types, or more than two of either type, are possible as well.While the sub-electrodes in the embodiment described herein areindependent for clear measurement of their respective currents, in oneembodiment, the main counter-reference electrode is connected at a baseand has two extending arms. In this embodiment, slight changes incurrent are measured at the moment the sample contacts each arm todetermine the fill time of the sample. Counter and reference electrodefunctions may be served by a single counter-reference electrode, andthere may be more than one working electrode, reference electrode, andcounter electrode. Some or all electrodes of a given test strip may bepositioned side-by-side on the same surface of a substrate, or ondifferent surfaces of a substrate, or some or all may be present onanother, e.g., second substrate. Additionally, some or all electrodesmay be stacked together, may include different materials and dimensions.

Current flows at the displaced electrodes are temporally separated bythe fill time. Recently-developed test strips, such as the those for theFreeStyle® blood glucose monitoring device, have three independentcounter-reference sub-electrodes, as illustrated in FIGS. 3A and 3B, sotwo different characteristic fill times can be determined: (1) t1=timefrom the first sub-electrode 118 to second sub-reference 120, and (2)t2=time from second sub-reference 120 to the third sub-electrode 122, aswell as their sum (t3=t2+t1). Fill time data determined from a teststrip (e.g., a FreeStyle® test strip) may therefore be used to correctthe blood glucose results and thereby reduce the hematocrit dependence.

The dependence of fill time on hematocrit is illustrated in theembodiment of FIG. 4, in which FreeStyle® test strips were tested at avariety of hematocrit values 132, while their fill times 134 wereplotted 136 and glucose-related signals were measured (see FIG. 5).

As depicted in FIG. 4, there is a consistent relationship between filltime 134 and hematocrit 132, with fill time 134 increasing as hematocrit132 increases. Next, the unit charge 138, or response, in uCcharge/mg/dL glucose (microCoulombs charge per milligram per deciliterof glucose) for these same strips is plotted in FIG. 5.

Again, the unit charge 138 (proportional to glucose) is elevated at lowhematocrit values 140, as depicted by the first measured charge 142, andthe unit charge 138 is depressed at high hematocrit values 140, asdepicted by the last measured response 144. The measured dependence ofthe unit response 138 on hematocrit 140, from the slope of the linearregression 146, is about 0.44 percent per hematocrit unit. It isdesirable that this slope 146 be decreased, such that the response isnot affected by hematocrit.

In accordance with embodiments of the invention, the fill timeinformation is incorporated into the response data in order to correctthe response data and lessen its dependence on hematocrit. In oneembodiment, the response data is corrected according to the followingequation: R_(c)=R_(r)+((Fill time−0.4 s)*R_(r)), where R_(r) equals theuncorrected response, and Rc equals the corrected response. The value of“(Fill time−0.4 s)” is limited to values less than or equal to 0.2, suchthat if (Fill time−0.4 s)>0.2, its value is set equal to 0.2. In effect,this limits the positive correction to 20 percent or less.

The plot of the corrected response factor is shown in FIG. 6. Note thatthis correction greatly reduces the dependence of the unit charge 138upon the hematocrit value 140 (the slope of the linear regression 148),from 0.44 percent/hematocrit unit to 0.09 percent/hematocrit unit.Therefore, “hematocrit correction,” or application of fill data tocorrect blood glucose measurements, has successfully reduced thedependence of the glucose measurement upon hematocrit.

In one embodiment, it is determined that a sample is a control solutionby using fill times of test strips to provide a determination that thesample is a control solution. Since a control solution is equivalent toa blood sample with very low or no hematocrit and therefore the controlsolution will fill the test strip rapidly

One skilled in the art will appreciate that there are many possiblemathematical formulations for determining hematocrit correction, and theequation above is merely an exemplary embodiment. In another embodiment,corrections might be calculated using another of the fill time valuesavailable from a test strip, if the test strip provides for multiplefill time measurements.

Additionally, one skilled in the art will appreciate that the test stripdoes not have to be electrochemical to measure the fill time. In oneembodiment, an optical measurement system could be implemented todetermine the fill time of the sample on the test strip. Furthermore, inan alternate embodiment, a test module could be used to measure the filltime instead of a test strip. The test module would measure the filltime without the use of a strip, and could be configured to makemultiple fill time measurements over time, such as in a laboratory orother clinical setting. The test module could implement an optical orelectrochemical measurement system.

In certain embodiments temperature may also affect viscosity (andtherefore fill time). Therefore, hematocrit correction based on filltime may also include accurate temperature measurement and compensation.In general, viscosity has in inverse relationship with temperature. Astemperature increases, viscosity decreases, and vice versa. Therefore,strips will fill faster at high temperature than at low temperature, ifall other factors (chiefly hematocrit) are equal. Fortunately,temperature can be accurately measured and temperature compensation ofviscosity is fairly straightforward. The ambient temperature as measuredby a temperature sensor in the meter is generally used. The strips aregenerally at the same temperature as the meter, and the thermal mass ofthe strips is large compared to the blood sample, so the blood sample isvery close to the same temperature as the meter.

In certain embodiments it is also necessary for the blood sample 110 tocompletely fill the test strip sample area 130 in order to obtain anaccurate fill time result, as show in FIG. 3B. A completely filled teststrip means the blood sample 110 must contact at least the two of thesub-electrodes, 118 and 122, and the intervening space between them.

Various aspects of embodiments the present invention, whether alone orin combination with other aspects of the invention, may be implementedin C++ code running on a computing platform operating in a LSB 2.0 Linuxenvironment. However, aspects of the invention provided herein may beimplemented in other programming languages adapted to operate in otheroperating system environments. Further, methodologies may be implementedin any type of computing platform, including but not limited to,personal computers, mini-computers, main-frames, workstations, networkedor distributed computing environments, computer platforms separate,integral to, or in communication with charged particle tools, and thelike. Further, aspects of the present invention may be implemented inmachine readable code provided in any memory medium, whether removableor integral to the computing platform, such as a hard disc, optical readand/or write storage mediums, RAM, ROM, and the like. Moreover, machinereadable code, or portions thereof, may be transmitted over a wired orwireless network.

Finally, it should be understood that processes and techniques describedherein are not inherently related to any particular apparatus and may beimplemented by any suitable combination of components. Further, varioustypes of general purpose devices may be used in accordance with theteachings described herein. It may also prove advantageous to constructspecialized apparatus to perform the method steps described herein. Thepresent invention has been described in relation to particular examples,which are intended in all respects to be illustrative rather thanrestrictive. It is intended that the specification and examples beconsidered as exemplary only, with a true scope and spirit of theinvention being indicated by the following claims.

1. A method of determining a hematocrit-corrected value, the methodcomprising: contacting a test strip with a sample that includes ananalyte; determining the fill time of the sample on the test strip; anddetermining a hematocrit-corrected value of the analyte using thedetermined fill time.
 2. The method of claim 1, comprising determiningthe hematocrit-corrected value of an analyte in a sample of blood. 3.The method of claim 2, comprising determining a hematocrit-correctedvalue of glucose.
 4. The method of claim 1, comprising determining thefill time of the sample on the test strip using a coulometric method. 5.The method of claim 1, comprising determining the fill time of thesample on the test strip using an amperometric method.
 6. The method ofclaim 1, wherein the test strip is adapted to provide a result usingless than about 1 microliter or less of sample.
 7. The method of claim1, comprising configuring the test strip with one working electrode andone counter-reference electrode.
 8. The method of claim 7, furthercomprising dividing the working electrode or the counter-referenceelectrode into two independent sub-electrodes: a first sub-electrode anda second sub-electrode.
 9. The method of claim 8, comprising determiningthe fill time of the test strip by calculating the time for the sampleto travel between the first sub-electrode and the second sub-electrode.10. The method of claim 7, further comprising dividing the workingelectrode or the counter-reference electrode into three independentsub-electrodes: a first sub-electrode, a second sub-electrode, and athirst sub-electrode.
 11. The method of claim 10, comprising determiningthree different fill times on the test strip, wherein a first fill timeis calculated between the first sub-electrode and the secondsub-electrode, a second fill time is calculated between the secondsub-electrode and the third sub-electrode, and wherein a third fill timeis calculated between the first sub-electrode and the thirdsub-electrode.
 12. A method for correcting the effect of hematocrit onblood glucose measurements, comprising: filling an electrochemical teststrip with a blood sample to be measured; wherein the test strip isconfigured to determine the fill time using electrochemical currentmeasurements; measuring the fill time of the sample on the test strip;determining an initial blood glucose concentration of the sample; andcalculating a corrected blood glucose concentration of the sample tocorrect for the effect of hematocrit upon blood glucose measurements byusing the fill time to estimate the hematocrit.
 13. A system todetermine a hematocrit-corrected value of an analyte, the systemcomprising: a test strip for contacting a sample; a meter adapted toreceive the test strip, determine a sample fill time of the test stripand determine a hematocrit-corrected value using the determined filltime.
 14. The system of claim 13, wherein the analyte is glucose. 15.The system of claim 14, wherein the sample is blood.
 16. The system ofclaim 15, wherein the system is adapted to provide ahematocrit-corrected value using about 1 microliter or less of thesample.
 17. The system of claim 11, wherein the meter uses a coulometricmethod to calculate the hematocrit-corrected value of the analyte. 18.The system of claim 11, wherein the meter uses a amperometric method tocalculate the hematocrit-corrected value of the analyte.
 19. The systemof claim 18, wherein the test strip further comprises a workingelectrode and a counter-reference electrode, and wherein the workingelectrode or the counter-reference electrode is divided into at leasttwo independent sub-electrodes.
 20. The system of claim 19, wherein theat least three independent sub-electrodes measure the time required fora sample to move across the test strip from a first sub-electrode to asecond sub-electrode, thereby calculating a fill time.
 21. A method ofdetermining a whether a sample is a control solution, the methodcomprising: contacting a test strip with a sample that includes ananalyte; determining the fill time of the sample on the test strip; anddetermining whether a sample is a control solution using the determinedfill time.
 22. The method of claim 21, comprising determining the filltime of the sample on the test strip using a coulometric method.
 23. Themethod of claim 21, comprising determining the fill time of the sampleon the test strip using an amperometric method.
 24. The method of claim21, wherein the test strip is adapted to provide a result using lessthan about 1 microliter or less of sample.
 25. The method of claim 21,comprising configuring the test strip with one working electrode and onecounter-reference electrode.
 26. The method of claim 25, furthercomprising dividing the working electrode or the counter-referenceelectrode into two independent sub-electrodes: a first sub-electrode anda second sub-electrode.
 27. The method of claim 26, comprisingdetermining the fill time of the test strip by calculating the time forthe sample to travel between the first sub-electrode and the secondsub-electrode.
 28. The method of claim 25, further comprising dividingthe working electrode or the counter-reference electrode into threeindependent sub-electrodes: a first sub-electrode, a secondsub-electrode, and a thirst sub-electrode.
 29. The method of claim 28,comprising determining three different fill times on the test strip,wherein a first fill time is calculated between the first sub-electrodeand the second sub-electrode, a second fill time is calculated betweenthe second sub-electrode and the third sub-electrode, and wherein athird fill time is calculated between the first sub-electrode and thethird sub-electrode.